Vanilloid receptors presynaptically modulate cranial visceral afferent synaptic transmission in nucleus tractus solitarius

Mark W. Doyle, Timothy W. Bailey, Young Ho Jin, Michael C. Andresen

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123 Scopus citations


Although the central terminals of cranial visceral afferents express vanilloid receptor 1 (VR1), little is known about their functional properties at this first synapse within the nucleus tractus solitarius (NTS). Here, we examined whether VR1 modulates afferent synaptic transmission. In horizontal brainstem slices, solitary tract (ST) activation evoked EPSCs. Monosynaptic EPSCs had low synaptic jitter (SD of latency to successive shocks) averaging 84.03 ± 3.74 μsec (n = 72) and were completely blocked by the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX). Sustained exposure to the VR1 agonist capsaicin (CAP; 100 nM) blocked ST EPSCs in neurons but not in some neurons but not others (CAP-resistant). CAP-sensitive EPSCs had longer latencies than CAP-resistant EPSCs (4.65 ± 0.27 msec, n = 48 vs 3.53 ± 01.28 msec, n = 24, respectively; p = 0.011), but they had similar jitter. CAP evoked two transient responses in CAP-sensitive neurons: a rapidly developing inward current (Icap (108.1 ± 22.9 pA; n = 21) and an increase in spontaneous synaptic activity. After 3-5 min in CAP Icap subsided and ST EPSCs disappeared. NBQX completely blocked Icap. The VR1 antagonist capsazepine (10-20 μm) attenuated CAP responses. Anatomically, second-order NTS neurons were identified by 4-(4-dihexadecylamino)styryl)-N-methylpyridinium ioclide transported from the cervical aortic depressor nerve (ADN) to stain central terminals. Neurons with fluorescent ADN contacts had CAP-sensitive EPSCs (n = 5) with latencies and jitter similar to those of unlabeled monosynaptic neurons. Thus, consistent with presynaptic VR1 localization, CAP selectively activates a subset of ST axons to release glutamate that acts on non-NMDA receptors. Because the CAP sensitivity of cranial afferents is exclusively associated with unmyelinated axons, VR1 identifies C-fiber afferent pathways within the brainstem.

Original languageEnglish (US)
Pages (from-to)8222-8229
Number of pages8
JournalJournal of Neuroscience
Issue number18
StatePublished - Sep 15 2002


  • Autonomic
  • Baroreceptor
  • Baroreflex
  • Glutamate
  • Presynaptic modulation
  • Sensory
  • Vanilloid
  • Visceral

ASJC Scopus subject areas

  • Neuroscience(all)


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